Antimicrobial Use and Resistance (AUR) Module
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Medical Review(S) Clinical Review
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 200327 MEDICAL REVIEW(S) CLINICAL REVIEW Application Type NDA Application Number(s) 200327 Priority or Standard Standard Submit Date(s) December 29, 2009 Received Date(s) December 30, 2009 PDUFA Goal Date October 30, 2010 Division / Office Division of Anti-Infective and Ophthalmology Products Office of Antimicrobial Products Reviewer Name(s) Ariel Ramirez Porcalla, MD, MPH Neil Rellosa, MD Review Completion October 29, 2010 Date Established Name Ceftaroline fosamil for injection (Proposed) Trade Name Teflaro Therapeutic Class Cephalosporin; ß-lactams Applicant Cerexa, Inc. Forest Laboratories, Inc. Formulation(s) 400 mg/vial and 600 mg/vial Intravenous Dosing Regimen 600 mg every 12 hours by IV infusion Indication(s) Acute Bacterial Skin and Skin Structure Infection (ABSSSI); Community-acquired Bacterial Pneumonia (CABP) Intended Population(s) Adults ≥ 18 years of age Template Version: March 6, 2009 Reference ID: 2857265 Clinical Review Ariel Ramirez Porcalla, MD, MPH Neil Rellosa, MD NDA 200327: Teflaro (ceftaroline fosamil) Table of Contents 1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT ......................................... 9 1.1 Recommendation on Regulatory Action ........................................................... 10 1.2 Risk Benefit Assessment.................................................................................. 10 1.3 Recommendations for Postmarketing Risk Evaluation and Mitigation Strategies ........................................................................................................................ -
Use of Ceftaroline Fosamil in Children: Review of Current Knowledge and Its Application
Infect Dis Ther (2017) 6:57–67 DOI 10.1007/s40121-016-0144-8 REVIEW Use of Ceftaroline Fosamil in Children: Review of Current Knowledge and its Application Juwon Yim . Leah M. Molloy . Jason G. Newland Received: November 10, 2016 / Published online: December 30, 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com ABSTRACT infections, CABP caused by penicillin- and ceftriaxone-resistant S. pneumoniae and Ceftaroline is a novel cephalosporin recently resistant Gram-positive infections that fail approved in children for treatment of acute first-line antimicrobial agents. However, bacterial skin and soft tissue infections and limited data are available on tolerability in community-acquired bacterial pneumonia neonates and infants younger than 2 months (CABP) caused by methicillin-resistant of age, and on pharmacokinetic characteristics Staphylococcus aureus, Streptococcus pneumoniae in children with chronic medical conditions and other susceptible bacteria. With a favorable and those with invasive, complicated tolerability profile and efficacy proven in infections. In this review, the microbiological pediatric patients and excellent in vitro profile of ceftaroline, its mechanism of action, activity against resistant Gram-positive and and pharmacokinetic profile will be presented. Gram-negative bacteria, ceftaroline may serve Additionally, clinical evidence for use in as a therapeutic option for polymicrobial pediatric patients and proposed place in therapy is discussed. Enhanced content To view enhanced content for this article go to http://www.medengine.com/Redeem/ 1F47F0601BB3F2DD. Keywords: Antibiotic resistance; Ceftaroline J. Yim (&) fosamil; Children; Methicillin-resistant St. John Hospital and Medical Center, Detroit, MI, Staphylococcus aureus; Streptococcus pneumoniae USA e-mail: [email protected] L. -
Chapter 12 Antimicrobial Therapy Antibiotics
Chapter 12 Antimicrobial Therapy Topics: • Ideal drug - Antimicrobial Therapy - Selective Toxicity • Terminology - Survey of Antimicrobial Drug • Antibiotics - Microbial Drug Resistance - Drug and Host Interaction An ideal antimicrobic: Chemotherapy is the use of any chemical - soluble in body fluids, agent in the treatment of disease. - selectively toxic , - nonallergenic, A chemotherapeutic agent or drug is any - reasonable half life (maintained at a chemical agent used in medical practice. constant therapeutic concentration) An antibiotic agent is usually considered to - unlikely to elicit resistance, be a chemical substance made by a - has a long shelf life, microorganism that can inhibit the growth or - reasonably priced. kill microorganisms. There is no ideal antimicrobic An antimicrobic or antimicrobial agent is Selective Toxicity - Drugs that specifically target a chemical substance similar to an microbial processes, and not the human host’s. antibiotic, but may be synthetic. Antibiotics Spectrum of antibiotics and targets • Naturally occurring antimicrobials – Metabolic products of bacteria and fungi – Reduce competition for nutrients and space • Bacteria – Streptomyces, Bacillus, • Molds – Penicillium, Cephalosporium * * 1 The mechanism of action for different 5 General Mechanisms of Action for antimicrobial drug targets in bacterial cells Antibiotics - Inhibition of Cell Wall Synthesis - Disruption of Cell Membrane Function - Inhibition of Protein Synthesis - Inhibition of Nucleic Acid Synthesis - Anti-metabolic activity Antibiotics -
Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications
International Journal of Molecular Sciences Review Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications Daniel Fernández-Villa 1, Maria Rosa Aguilar 1,2 and Luis Rojo 1,2,* 1 Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, CSIC, 28006 Madrid, Spain; [email protected] (D.F.-V.); [email protected] (M.R.A.) 2 Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-622-900 Received: 18 September 2019; Accepted: 7 October 2019; Published: 9 October 2019 Abstract: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Keywords: folic acid antagonists; antifolates; antibiotics; antibacterials; immunomodulation; sulfonamides; antimalarial 1. -
Empiric Antimicrobial Therapy for Diabetic Foot Infection
Empiric Antimicrobial Therapy for Diabetic Foot Infection (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2019) Infection Severity Preferred Empiric Regimens Alternative Regimens Comments Mild Wound less than 4 weeks duration:d Wound less than 4 weeks duration:e • Outpatient management • Cellulitis less than 2 cm and • cephalexin 500 – 1000 mg PO q6h*,a OR • clindamycin 300 – 450 mg PO q6h (only if recommended ,a • cefadroxil 500 – 1000 mg PO q12h* severe delayed reaction to a beta-lactam) without involvement of deeper • Tailor regimen based on culture tissues and susceptibility results and True immediate allergy to a beta-lactam at MRSA Suspected: • Non-limb threatening patient response risk of cross reactivity with cephalexin or • doxycycline 200 mg PO for 1 dose then • No signs of sepsis cefadroxil: 100 mg PO q12h OR • cefuroxime 500 mg PO q8–12h*,b • sulfamethoxazole+trimethoprim 800+160 mg to 1600+320 mg PO q12h*,f Wound greater than 4 weeks duration:d Wound greater than 4 weeks duratione • amoxicillin+clavulanate 875/125 mg PO and MRSA suspected: q12h*,c OR • doxycycline 200 mg PO for 1 dose then • cefuroxime 500 mg PO q8–12h*,b AND 100 mg PO q12h AND metroNIDAZOLE metroNIDAZOLE 500 mg PO q12h 500 mg PO q12h OR • sulfamethoxazole+trimethoprim 800+160 mg to 1600/320 mg PO q12h*,f AND metroNIDAZOLE 500 mg PO q12h Moderate Wound less than 4 weeks duration:d Wound less than 4 weeks duration:e • Initial management with • Cellulitis greater than 2 cm or • ceFAZolin 2 g IV q8h*,b OR • levoFLOXacin 750 -
Unexpected Induction of Resistant Pseudomonas Aeruginosa Biofilm to fluoroquinolones by Diltiazem: a New Perspective of Microbiological Drug—Drug Interactionଝ
Journal of Infection and Public Health (2008) 1, 105—112 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Unexpected induction of resistant Pseudomonas aeruginosa biofilm to fluoroquinolones by diltiazem: A new perspective of microbiological drug—drug interactionଝ Walid F. ElKhatib, Virginia L. Haynes, Ayman M. Noreddin ∗ University of Minnesota, Duluth, College of Pharmacy, Pharmacy Practice and Pharmaceutical Sciences, 1110 Kirby Dr. Life Sciences 232, Duluth, MN 55812, USA Received 15 August 2008; received in revised form 21 October 2008; accepted 22 October 2008 KEYWORDS Summary The increase of multi-drug resistant Pseudomonas aeruginosa infec- Diltiazem; tions is a worldwide dilemma. At the heart of the problem is the inability to treat Pseudomonas established P. aeruginosa biofilms with standard antibiotic therapy, including flu- aeruginosa; oroquinolones. We address a previously unstudied question as to the effect of a Biofilm; commonly prescribed calcium channel blocker (CCB) diltiazem on the biofilm growth. Resistance; Real-time monitoring of the overall growth and killing of P.aeruginosa biofilm during fluoroquinolones therapy in the presence and absence of diltiazem was performed. Fluoroquinolone In this study, we demonstrate that for P. aeruginosa biofilms, resistance to the first- line fluoroquinolones may be induced by the commonly prescribed calcium channel blocker diltiazem. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. All rights reserved. Introduction approved for the treatment of angina, hyper- tension and cardiac arrhythmia [1]. It acts as Diltiazem is a class III calcium channel blocker a calcium antagonist that controls calcium ion (CCB) belonging to benzothiazepines and has been influx in cardiac and vascular smooth muscle cells through slow voltage-gated L-type channels in the ଝ This manuscript was presented in part at the Design of Med- cell membrane. -
Activity of Cefepime-Zidebactam Against Multidrug-Resistant (MDR) Gram-Negative Pathogens
antibiotics Article Activity of Cefepime-Zidebactam against Multidrug-Resistant (MDR) Gram-Negative Pathogens Kenneth S. Thomson 1,* , Sameh AbdelGhani 1,2, James W. Snyder 1 and Gina K. Thomson 1,3 1 Department of Pathology and Laboratory Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA; [email protected] (S.A.); [email protected] (J.W.S.); [email protected] (G.K.T.) 2 Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt 3 Microbiology Department, University of Louisville Hospital, Louisville, KY 40202, USA * Correspondence: [email protected] Received: 18 February 2019; Accepted: 19 March 2019; Published: 23 March 2019 Abstract: This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected currently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates chosen to provide an extreme challenge for antibacterial activity. FEP–ZID had a very broad and potent in vitro spectrum of activity, and was highly active against many MDR isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Notably, it inhibited isolates producing carbapenemases of Ambler classes A, B, and D, and P. aeruginosa isolates with multiple resistance mechanisms including combinations of upregulated efflux, diminished or non-functional OprD porins, and AmpC overproduction. Its clinical role will be determined initially by the breakpoints assigned to it, comparison studies with other investigational β-lactamase inhibitor combinations, and ultimately by the developing body of therapeutic outcome data. Keywords: carbapenemase-producing organism; carbapenemase; zidebactam; therapy 1. Introduction Gram-negative multidrug-resistant (MDR) pathogens, particularly carbapenemase-producing organisms (CPOs), cause infections of high mortality that are typically treated with antibiotic combinations that include toxic drugs such as polymyxins and aminoglycosides [1]. -
Structure of a Penicillin Binding Protein Complexed with a Cephalosporin-Peptidoglycan Mimic M.A
Structure of a Penicillin Binding Protein Complexed with a Cephalosporin-Peptidoglycan Mimic M.A. McDonough1, W. Lee2, N.R. Silvaggi1, L.P. Kotra 2, Z-H. Li2, Y. Takeda2, S .O. Mobashery2, and J.A. Kelly1 1Department of Molecular and Cell Biology and Institute for Materials Science, Univ. of Connecticut, Storrs, CT 2Institute for Drug Design and the Department of Chemistry, Wayne State Univ., Detroit, MI Many bacteria that are responsible for causing dis- lactams. Also, one questions why ß-lactamases hydro- eases in humans are rapidly developing mutant strains lyze ß-lactams and release them rapidly but they do resistant to existing antibiotics. Proliferation of these not react with peptide substrates. mutant strains is likely to be a serious health-care prob- To help answer these questions, structural studies lem of increasing proportions. Almost sixty percent of of the Streptomyces sp. R61 D-Ala-D-Ala-peptidase all clinically used antibiotics are beta-lactams, which have been undertaken to investigate how the enzyme stop the growth of bacteria by interfering with their cell- wall biosynthesis. The cell walls are made of glycan chains that polymerize to form a structure that gives strength and shape to the bacteria. An understanding of the process how the cell wall is synthesized may help in designing more potent antibiotics. D-Ala-D-Ala-carboxypeptidase/transpeptidases (DD-peptidases) are penicillin-binding proteins (PBPs), the targets of ß-lactam antibiotics such as penicillins and cephalosporins (Figure 1A). These enzymes cata- lyze the final cross-linking step of bacterial cell wall bio- synthesis. In vivo inhibition of PBPs by ß-lactams re- sults in the cessation of bacterial growth. -
UNASYN® (Ampicillin Sodium/Sulbactam Sodium)
® UNASYN (ampicillin sodium/sulbactam sodium) To reduce the development of drug-resistant bacteria and maintain the effectiveness of UNASYN® and other antibacterial drugs, UNASYN should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. DESCRIPTION UNASYN is an injectable antibacterial combination consisting of the semisynthetic antibacterial ampicillin sodium and the beta-lactamase inhibitor sulbactam sodium for intravenous and intramuscular administration. Ampicillin sodium is derived from the penicillin nucleus, 6-aminopenicillanic acid. Chemically, it is monosodium (2S, 5R, 6R)-6-[(R)-2-amino-2-phenylacetamido]-3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate and has a molecular weight of 371.39. Its chemical formula is C16H18N3NaO4S. The structural formula is: COONa O CH 3 N CH O 3 NH S NH 2 1 Reference ID: 4053909 Sulbactam sodium is a derivative of the basic penicillin nucleus. Chemically, sulbactam sodium is sodium penicillinate sulfone; sodium (2S, 5R)-3,3-dimethyl-7-oxo-4-thia- 1-azabicyclo [3.2.0] heptane-2-carboxylate 4,4-dioxide. Its chemical formula is C8H10NNaO5S with a molecular weight of 255.22. The structural formula is: COONa CH 3 O N CH 3 S O O UNASYN, ampicillin sodium/sulbactam sodium parenteral combination, is available as a white to off-white dry powder for reconstitution. UNASYN dry powder is freely soluble in aqueous diluents to yield pale yellow to yellow solutions containing ampicillin sodium and sulbactam sodium equivalent to 250 mg ampicillin per mL and 125 mg sulbactam per mL. The pH of the solutions is between 8.0 and 10.0. -
Simultaneous Determination of Amoxicillin and Clavulanic Acid in Pharmaceutical Preparations by Capillary Zone Electrophoresis
Brazilian Journal of Pharmaceutical Sciences vol. 52, n. 2, apr./jun., 2016 Article http://dx.doi.org/10.1590/S1984-82502016000200006 Simultaneous determination of amoxicillin and clavulanic acid in pharmaceutical preparations by capillary zone electrophoresis Gabriel Hancu1,*, Anamaria Neacşu1, Lajos Attila Papp1, Adriana Ciurba2 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, TîrguMureş, Romania, 2Department of PharmaceuticalTechnology, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most β-lactamase producing isolates susceptible to the drug. A fast, simple and efficient capillary electrophoresis method was developed for the simultaneous determination of amoxicillin and clavulanic acid from complex mixtures. Using a 25 mM sodium tetraborate as background electrolyte at a pH of 9.30, + 25 kV applied voltage, 25 °C system temperature, UV determination at 230 nm; we succeeded in simultaneous separation of amoxicillin and clavulanic acid in approximately 2 minutes. The analytical performance of the method was evaluated in terms of reproducibility, precision, accuracy, and linearity. The optimized analytical method was applied for the determination of the two analytes from combined commercial pharmaceutical preparations. This CE method is fast, inexpensive, efficient, and environmentally friendly when compared with the more frequently used high performance liquid chromatography methods described in the literature. Uniterms: Amoxicillin/determination. Clavulanic acid/determination. Capillary electrophoresis/ quantitative analysis. Antibacterials/quantitative analysis. O ácido clavulânico acentua o espectro antibacteriano de amoxicilina, tornando a maioria dos isolados produtores de β-lactamase sensíveis ao fármaco. Desenvolveu-se um método rápido, simples e eficiente de electroforese capilar (EC) para a determinação simultânea de amoxicilina e de ácido clavulânico a partir de misturas complexas. -
Plazomicin Sulfate ASHP INJECTABLE DRUG INFORMATION
1302 PLAZOMICIN SULFATE ASHP INJECTABLE DRUG INFORMATION Plazomicin Sulfate AHFS 8:12.02 Products Stability Plazomicin sulfate is available in a concentration equivalent Intact vials of plazomicin sulfate should be stored under refrig- to plazomicin base 50 mg/mL in 10-mL single-dose (preserva- eration at 2 to 8°C.3431 Plazomicin sulfate injection is a clear, tive-free) vials.3431 Each vial also contains sodium hydroxide colorless to yellow solution.3431 The manufacturer states that for pH adjustment and water for injection.3431 The appropriate the solution may become yellow, but that this change does not dose of plazomicin solution should be diluted in sodium chloride indicate a decrease in potency.3431 0.9% or Ringer’s injection, lactated to achieve a final volume of The manufacturer states that a solution of plazomicin diluted 3431 50 mL. for infusion in sodium chloride 0.9% or Ringer’s injection, pH lactated to concentrations of 2.5 to 45 mg/mL is stable for up to 24 hours at room temperature.3431 Adjusted to 6.5.3431 Trade Name(s) Zemdri Administration Plazomicin sulfate is administered by intravenous infusion over 30 minutes after dilution in sodium chloride 0.9% or Ringer’s injection, lactated.3431 Compatibility Information Solution Compatibility Plazomicin sulfate Test Soln Name Mfr Mfr Conc/L or % Remarks Ref C/I Ringer’s injection, lactated ACH 2.5 to 45 g Stable for 24 hr at room temperature 3431 C Sodium chloride 0.9% ACH 2.5 to 45 g Stable for 24 hr at room temperature 3431 C Y-Site Injection Compatibility (1:1 Mixture) Plazomicin -
The Pharmacodynamics of Plazomicin and Amikacin Studied in an in Vitro
P203 The pharmacodynamics of plazomicin and amikacin studied in an in vitro pharmacokinetic model Karen E Bowker 1, Alan R Noel 1, Marie A Attwood 1, Sharon G Tomaselli 1, Alasdair P MacGowan 1, Kevin Krause 2, Eileen Kim 2 BCARE, Department of Microbiology, North Bristol NHS Trust, Bristol, UK. 1 Achaogen Inc, South San Francisco, California, USA 2 [email protected] ASM MICROBE, New Orleans, 1-5th June, 2017 Introduction Results The AUC/MIC targets for amikacin administered 12hrly against E.coli (n=3) Aminoglycoside antibiotics have been a mainstay of antimicrobial Table 3: Individual and mean AUC/MIC targets for K.pneumoniae for were 12h static effect 16.1±10; -1 log drop 22.8±12.5; -2 log drop 32.4±12.4; chemotherapy for more than forty years yet the pre-clinical data on their plazomicin administered 12hrly pharmacokinetics-pharmacodynamics (PK-PD) is scarce. -3 log drop 59.3±11.9; 24h static effect 49.5±12.7; -1 log drop 55.7±14.8; -2 Endpoint strain AUC/MIC Published data points to AUC/MIC or Cmax/MIC as the dominant log drop 64.1±19.5; -3 log drop 73.3±25.3; 48hr static effect 78.6±35.9; -1 AKPN 1169 AKPN 1170 AKPN 1171 KP41965 KP41966 Mean ± STD pharmacodynamic index (PDI) with an AUC/MIC of 50-70 being associated log drop 81.0±36.6; -2 log drop 81.8±37.8; -3 log drop 84.2±38.9. 12h with 24h static effect for aerobic Gram-negative rods ( Enterobacteriaceae The AUC/MIC targets for plazomicin and amikacin against E.coli when 24h Static 15.2 66.1 40.7 37.6 17.2 35.3±20.7 -1 log drop 28.8 77.6 49.6 59.3 23.7 47.8±22.2 and Pseudomonas aeruginosa ).